Neuropathology of late life depression: Clinical predictors of amyloid and tau neuropathology in non‐demented older adults with depression.

Background: Previous studies regarding the relationship between depression and amyloid and tau neuropathology have reported conflicting findings. We examined whether depression is associated with higher Alzheimer's disease neuropathologic changes and whether sex moderates their relationships. Method: Using the National Alzheimer's Coordinating Center database (2005‐2020), we conducted a cross‐sectional study of non‐demented older adults (age 50+; CDR ≤ 0.5) who had autopsy within 1 year of their last clinic visit. Multivariable cumulative logit models were fitted to determine if recent and/or remote depression were associated with Thal phase score (a measure of spread of amyloid plaques) modified according to National Institute on Aging–Alzheimer's Association (NIA‐AA) guidelines, modified Braak stage for neurofibrillary degeneration according to NIA‐AA guidelines, density of neuritic plaques [CERAD score] and if any of their associations were moderated by sex. All regression models were adjusted for covariates associated with both depression and Alzheimer's disease, including selective serotonin or serotonin norepinephrine reuptake inhibitor use, sex, age, years of education, the presence of apolipoprotein E e4 allele, and history of diabetes, hypertension, hypercholesteremia, and traumatic brain injury. Result: We included 395 participants (94 Thal, 393 Braak, and 394 CERAD). Those who had recent (within previous 2 years) but not remote depression were more likely to have higher Thal phase compared to those without a history of depression (Odds Ratio = 13.3; 95% CI, 1.5‐116.3, p = 0.019). Sex did not moderate the association between recent depression and Thal phase. No significant associations between depression and Braak or CERAD scores were observed. Conclusion: Our findings suggest that recently active late‐life depression is associated with spread of amyloid pathology beyond cortical regions to include subcortical regions but not with density of neuritic plaques or neurofibrillary tangles. [ABSTRACT FROM AUTHOR]